JP2007230938A - Preventing or improving agent of alzheimer type memory disorder - Google Patents
Preventing or improving agent of alzheimer type memory disorder Download PDFInfo
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本発明は、脳内の神経回路網の破綻に起因する認識機能不全、特にアルツハイマー型記憶障害の予防・改善に有効な漢方処方に関するものである。 The present invention relates to a Kampo prescription effective for the prevention and improvement of cognitive dysfunction caused by the breakdown of a neural network in the brain, particularly Alzheimer's memory impairment.
日本は、急速に高齢化社会を迎えている。老化にともなう物忘は健忘症と称されるが、健忘症は、加齢に伴う生理的な変化であり病気ではない。一方、認知症と称される痴呆症は、一度獲得した知的能力が脳の後天的な変化により著しく低下した状態を呈する脳の病気である。痴呆症の代表的なものとしてアルツハイマー病、脳血管性痴呆が知られているが、アルツハイマー病は、進行性であり、未だ有効な治療法がないため、深刻な問題となっている。
病因が不明であり、種々の薬物による治療が試みられている。
Japan is rapidly facing an aging society. Amnesia associated with aging is called amnesia, but amnesia is a physiological change with age and is not a disease. On the other hand, dementia, called dementia, is a brain disease in which the intellectual ability once acquired is markedly reduced by acquired changes in the brain. Alzheimer's disease and cerebrovascular dementia are known as typical dementia, but Alzheimer's disease is a serious problem because it is progressive and there is still no effective treatment.
The etiology is unknown and treatment with various drugs has been attempted.
臨床で抗痴呆薬として用いられているドネペジルのようなコリンエステラーゼ阻害薬は、疾患の進行を遅らせるものの疾患を治療するには至らず、且つ中程度を超えた痴呆患者には有効性が現れにくい。また神経栄養因子様作用物質に分類される薬物も抗痴呆薬候補として研究されているが、いずれも神経保護作用が主であり、神経変成環境下における神経突起伸展作用とシナプス形成作用は明確に示されていない。 A cholinesterase inhibitor such as donepezil used clinically as an anti-dementia drug does not treat the disease although it delays the progression of the disease, and is hardly effective in patients with dementia exceeding moderate. Drugs classified as neurotrophic factor-like substances have also been studied as anti-dementia drug candidates, but all of them are mainly neuroprotective, and the neurite outgrowth and synapse formation in a neurodegenerative environment are clear. Not shown.
一方、漢方を基礎とする抗痴呆薬として、例えば、丹参、川きゅう、芍薬、紅花、木香、香附子を原料とした「冠元顆粒」（特許文献１）、芍薬、蒼朮、沢瀉、茯苓、川きゅう、当帰を原料とした「当帰芍薬散」（特許文献２）が知られており、また、人参（分量1）、遠志（分量2）、菖蒲（分量1）、白茯苓（分量3）からなる「定志円」が物忘れを治すことが、漢方処方の古典「丹渓心法」「備急千金要方」に記載されている。また、人参（分量1）、遠志（分量2）、菖蒲（分量25）、白茯苓（分量50）からなるDX-9386が動物実験において記憶障害を改善することが報告されている（非特許文献１）。また、人参、朮、茯苓、黄耆、当帰、遠志、柴胡、山梔子、甘草、木香、大棗、生姜、酸棗仁、龍眼肉からなる加味帰脾湯は、虚血性脳疾患を改善することが報告されている（特許文献３）。加味帰脾湯には他にも、ドネペジルとの併用療法によりアルツハイマー病患者の自発性障害と感情障害を改善する作用があることが示されている（非特許文献２）。また、加味帰脾湯から柴胡と山梔子を抜いた処方である帰脾湯は、老年期痴呆症患者に対して認知機能改善効果を示すことが報告されている（非特許文献３）。
一方、本発明者は、人参、黄耆、遠志が神経障害後から軸索および樹状突起の再形成、シナプスの再形成作用を有することを見出してきた。(非特許文献４)
On the other hand, as an anti-dementia drug based on Kampo medicine, for example, “crown granule” (Patent Document 1) made from Dansang, Kawakyu, glaze, safflower, wood incense, and Katsuki, raw material, glaze, acupuncture, buds, acupuncture , Kawakyu, “Tokien Yakusan” made from Toki (Patent Document 2) is also known, and carrot (1), distant (2), salmon (1), birch ( The classic “Tankeishin method” and “Bikkyu Senkin Kakata” of Chinese medicine prescriptions indicate that the “determined circle” consisting of 3) cures forgetfulness. In addition, it has been reported that DX-9386, which consists of carrot (part 1), distant (part 2), cocoon (part 25), and white rabbit (part 50), improves memory impairment in animal experiments (non-patent literature). 1). In addition, Kamikisui, which consists of carrots, carrots, sea breams, jaundice, Toki, Toshi, Saiko, Yamayoko, licorice, woody incense, Daegu, ginger, sour jelly and longan meat, improves ischemic brain disease (Patent Document 3). In addition, it has been shown that Kamikisuito has an effect of improving spontaneous disorder and emotional disorder in Alzheimer's disease patients by combination therapy with donepezil (Non-patent Document 2). In addition, it has been reported that Kisui-to, which is a prescription obtained by removing Saiko and Yamakiko from Kamiki-sui, has an effect of improving cognitive function in patients with senile dementia (Non-patent Document 3).
On the other hand, the present inventor has found that ginseng, jaundice, and distantness have axonal and dendritic remodeling and synaptic remodeling actions after neuropathy. (Non-Patent Document 4)
アルツハイマー病は、神経回路網の破綻により、記憶・認知に障害を呈する症候を指す。これら有効な治療法の無い疾患に対し、既に神経回路網の障害が進行している状態からでも、神経機能を正常に近づけることのできる治療が、真に求められている。しかも患者の立場を考えると、手術を要する神経細胞移植や遺伝子治療よりは、負担の少ない投薬による治療法がより望ましい。そこで、神経細胞が障害を受けている時、あるいは受けた後からでも神経回路網を再生する薬物の開発が必要である。
本発明は、神経回路網を再生する薬物を、すでに広く使用され安全性が十分に確認されている漢方薬から見出すことを目的とする。
Alzheimer's disease refers to symptoms that impair memory and cognition due to the breakdown of neural networks. For these diseases for which there is no effective therapeutic method, there is a real need for a treatment that can bring the nerve function closer to normal even when the nerve network has already been impaired. Moreover, considering the patient's standpoint, treatment with less burden is more desirable than nerve cell transplantation and gene therapy that require surgery. Therefore, it is necessary to develop a drug that regenerates the neural network even when the nerve cells are damaged or after the damage.
An object of the present invention is to find a drug that regenerates a neural network from a herbal medicine that has already been widely used and whose safety has been sufficiently confirmed.
本発明者らは、神経回路網の破綻の細胞モデルとして、ラット大脳皮質神経の初代培養細胞に、アルツハイマー病の原因物質であるアミロイドベータの活性部分配列（Ａβ（25-35））を処置し、軸索と樹状突起の萎縮、シナプス数の減少を呈する状態を作製した。この状態の神経細胞に処置することで、神経細胞の神経突起とシナプスを正常状態に戻すことのできる薬物を探索することができる。
探索方法は、例えば、試験薬物として、生薬を様々な配合比で合わせ、水で煎じ液エキスを作成し、それを上記の細胞モデルで試験する。この方法で、試験方剤エキスが神経突起伸展作用を有するかどうかを検討することができる。
さらに、本発明者らは、神経回路網の破綻の動物モデルとして、マウスの側脳室内にＡβ（25-35）を単回投与し、１週間後から現れ始める空間記憶障害と、脳内の軸索と樹状突起の萎縮、シナプス数の減少を呈する状態を作製した。
The present inventors treated an active partial sequence (Aβ (25-35)) of amyloid beta, which is a causative agent of Alzheimer's disease, in primary cultured cells of rat cerebral cortical nerves as a cell model of neural network failure. A state of atrophy of axons and dendrites, and a decrease in the number of synapses was prepared. By treating nerve cells in this state, it is possible to search for drugs that can return the neurites and synapses of the nerve cells to a normal state.
In the search method, for example, as a test drug, herbal medicines are combined at various compounding ratios, a decoction extract is prepared with water, and this is tested with the above cell model. By this method, it can be examined whether or not the test agent extract has a neurite extension action.
Furthermore, as an animal model of neural network failure, the present inventors administered Aβ (25-35) once in the lateral ventricle of a mouse, and spatial memory impairment that began to appear after one week, A state in which atrophy of axons and dendrites, and decrease in the number of synapses was produced.
上記、アッセイ系で、種々の漢方処方を検討した結果、健忘症に対して使用されている帰脾湯と称される漢方処方は、細胞モデルで、神経突起伸展作用が認められ、さらに動物モデルにおいても優れた効果が認められたことから、本発明を完成するに至った。以下、本発明を詳細に説明する。 As a result of examining various Kampo prescriptions in the above assay system, the Kampo prescription called Kaisei-to, which is used for amnesia, is a cell model and has a neurite outgrowth action. As a result, an excellent effect was recognized, and the present invention was completed. Hereinafter, the present invention will be described in detail.
本発明は、生薬としてオウギ（黄耆）、ニンジン（人参）、ビャクジュツ（白朮）、ブクリョウ（茯苓）、オンジ（遠志）、タイソウ（大棗）、トウキ（当帰）、カンゾウ（甘草）、ショウキョウ（生姜）、モッコウ（木香）、サンソウニン（酸棗仁）およびリュウガンニク（龍+眼肉）の混合物、その抽出物（エキス）および各生薬のエキスの混合物からなるアルツハイマー型記憶障害の予防・改善剤である。
より具体的には、黄耆1〜3重量部、人参1〜3重量部、白朮1〜3重量部、茯苓1〜3重量部、遠志1〜3重量部、大棗1〜3重量部、当帰1〜3重量部、甘草1〜3重量部、生姜1〜3重量部、木香1〜3重量部、酸棗仁1〜3重量部、龍眼肉1〜3重量部の生薬の混合物、そのエキスおよび各生薬エキスの混合物からなるアルツハイマー型記憶障害の予防・改善剤である。さらに具体的には、帰脾湯と称される漢方処方である。
In the present invention, as herbal medicines, ogi (carp), carrot (carrot), peanut (white cocoon), bukuro (cage), onji (distant), taisou (daegu), touki (toll), licorice (licorice), show Prevention / prevention of Alzheimer-type memory impairment consisting of a mixture of Kyo (ginger), mokko (scented incense), sansounin (acid soy sauce) and longannik (dragon + eye meat), its extract (extract) and a mixture of each herbal medicine It is an improving agent.
More specifically, 1 to 3 parts by weight of jaundice, 1 to 3 parts by weight of ginseng, 1 to 3 parts by weight of white ginseng, 1 to 3 parts by weight of cocoon, 1 to 3 parts by weight of ginger, 1 to 3 parts by weight of oak, A mixture of herbal medicines of 1 to 3 parts by weight, 1 to 3 parts by weight of licorice, 1 to 3 parts by weight of ginger, 1 to 3 parts by weight of incense, 1 to 3 parts by weight of sour bean, 1 to 3 parts by weight of longan meat, It is a preventive / improving agent for Alzheimer-type memory impairment consisting of a mixture of the extract and herbal extracts. More specifically, it is a Kampo prescription called Kaisui.
本発明において使用される生薬は以下のものである。
黄耆（オウギ）は、マメ科の多年草（Astragalus membranaceus BungeまたはAstragalus mongholicus Bunge）の根である。
人参（ニンジン）は、ウコギ科の多年草オタネニンジン（Panax ginseng C.A. Meyer）の根である。畑で収穫され、取れたばかりの人参は水参と呼ばれており、4〜6年根の水参を原料として、ほとんどは皮を剥ぎ、自然乾燥または60℃以下で熱風乾燥させて水分を15%以下としたものが白参、水参に蒸気を当てて蒸したものを乾燥したものが紅参と呼ばれている。
白朮（ビャクジュツ）は、キク科のオオバナオケラ（Atractylodes ovata DC.）の根茎である。
茯苓（ブクリョウ)は、サルノコシカケ科茯苓菌（Poria cocos（Schw.） Wolf.）（マツホド）の菌核である。菌核の内部が淡赤色ものが赤茯苓である。
遠志は（オンジ）、ヒメハギ科のイトヒメハギ（Polygala tenuifolia Willd.）の根である。
大棗（タイソウ）は、クロウメモドキ科のナツメ（Zizyphus jujube Mill. var. inermis (Bunge) Rehd.）またはその品種の果実である。
当帰は、セリ科のトウキ（Angelica acutiloba Kitagawa）、およびカラトウキ（Angelica sinensis (Oliv.) Diels）の根である。
甘草は、マメ科のナンキンカンゾウ（Glycyrrhiza glabra L. var. glandulifera Reg. et Herd.）およびウラルカンゾウ（Glycyrrhiza uralensis Fisch. ex DC.）の根およびストロンである。
生姜は、ショウガ科のショウガ（Zingiber officinale Roscoe）の根茎である。
木香（モッコウ）は、キク科の広木香（Saussurea lappa Clarke）の根である。
酸棗仁（サンソウニン）は、クロウメモドキ科のサネブトナツメ（Zizyphus jujube Mill. var. inermis (Bunge) Rehd.）の種子である。
龍眼肉（リュウガンニク）は、ムクロジ科のリュウガン（Euphoria longana Lam.）の仮種皮である。
The crude drugs used in the present invention are as follows.
The jade is the root of a leguminous perennial (Astragalus membranaceus Bunge or Astragalus mongholicus Bunge).
Carrot is the root of the perennial perennial ginseng (Panax ginseng CA Meyer). Ginseng harvested in the field and freshly picked is called daffodils. Most of the ginseng is made from 4-6 years root ginseng. What is less than% is called white ginseng, and what is steamed and dried from ginseng is called red ginseng.
White birch is a rhizome of Atractylodes ovata DC.
Bakuryo is the sclerotium of Poria cocos (Schw.) Wolf. (Matsuhod). The red cocoon inside the mycorrhiza is pale red.
Distant (Onji) is the root of Polygala tenuifolia Willd.
Taiso is the fruit of the family Zizyphus jujube Mill. Var. Inermis (Bunge) Rehd. Or its varieties.
This is the root of the celery family Angelica acutiloba Kitagawa and Karatouki (Angelica sinensis (Oliv.) Diels).
Licorice is the root and stron of leguminous licorice (Glycyrrhiza glabra L. var. Glandulifera Reg. Et Herd.) And Ural licorice (Glycyrrhiza uralensis Fisch. Ex DC.).
Ginger is the rhizome of Zingiber officinale Roscoe.
Mokuko is the root of Saussurea lappa Clarke.
Sunsounin is the seed of Zizyphus jujube Mill. Var. Inermis (Bunge) Rehd.
Longan meat is a temporary seed coat of Euphoria longana Lam.
本発明は、上記12種類の生薬の混合物、その抽出物（エキス）または12種類の生薬個々のエキスの混合物である。
混合物の配合は、黄耆1〜3重量部、人参1〜3重量部、白朮1〜3重量部、茯苓1〜3重量部、遠志1〜3重量部、大棗1〜3重量部、当帰1〜3重量部、甘草1〜3重量部、生姜1〜3重量部、木香1〜3重量部、酸棗仁1〜3重量部、龍眼肉1〜3重量部である。
好ましくは、黄耆2〜3重量部、人参2〜3重量部、白朮2〜3重量部、茯苓2〜3重量部、遠志1〜2重量部、大棗1〜2重量部、当帰2重量部、甘草1重量部、生姜1〜1.5重量部、酸棗仁2〜3重量部、木香1重量部、龍眼肉2〜3重量部である。
12種類の生薬を混合した抽出物（エキス）は、通常、混合物の10〜30倍量の水で熱時抽出(煎じ)し、乾燥して得られるものである。
乾燥方法は、凍結乾燥、温風乾燥など、通常の乾燥法を使用すればよい。
本発明の好ましい例として、黄耆3重量部、人參3重量部、白朮3重量部、茯苓3重量部、遠志2重量部、大棗2重量部、当帰2重量部、甘草1重量部、生姜1.5重量部、木香1重量部、酸棗仁3重量部、竜眼肉3重量部を混合し、20〜25倍量の水で混合物を1〜1.5時間煎じた後、煎じ液から不溶物をろ別し、ろ液を凍結乾燥して得られる粉末（以下、帰脾湯エキスと称する）が挙げられる。
The present invention is a mixture of the above 12 kinds of herbal medicines, an extract (extract) thereof, or a mixture of 12 kinds of herbal medicine individual extracts.
The mixture is composed of 1 to 3 parts by weight of jaundice, 1 to 3 parts by weight of ginseng, 1 to 3 parts by weight of white ginseng, 1 to 3 parts by weight of carp, 1 to 3 parts by weight of ginger, 1 to 3 parts by weight of sushi. 1 to 3 parts by weight, 1 to 3 parts by weight of licorice, 1 to 3 parts by weight of ginger, 1 to 3 parts by weight of incense, 1 to 3 parts by weight of soy sauce, and 1 to 3 parts by weight of longan.
Preferably, 2 to 3 parts by weight of jaundice, 2 to 3 parts by weight of ginseng, 2 to 3 parts by weight of white carp, 2 to 3 parts by weight of carp, 1 to 2 parts by weight of eagle, 1 to 2 parts by weight of oak,
An extract (extract) obtained by mixing 12 kinds of herbal medicines is usually obtained by hot extraction (decoction) with 10 to 30 times the amount of water of the mixture and drying.
As a drying method, a normal drying method such as freeze drying or hot air drying may be used.
As a preferred example of the present invention,
本発明の生薬混合物のエキスを医薬品とする場合、賦形剤、補助剤、添加剤などと組み合わせ、各種の医薬製剤、例えば、液剤、懸濁剤、シロップ剤、エリキシル剤、エキス剤、散剤、顆粒剤、細粒剤、錠剤、カプセル剤などにすればよい。
また、医薬品として投与する場合、投与方法、投与量および投与回数は、患者の年齢、体重および症状によって適宜選択できるが、経口投与の場合、エキスとして1〜1000mg/kg、好ましくは20〜100mg/ｋｇであればよい。
When the extract of the herbal medicine mixture of the present invention is used as a pharmaceutical product, it is combined with excipients, adjuvants, additives and the like, and various pharmaceutical preparations such as solutions, suspensions, syrups, elixirs, extracts, powders, Granules, fine granules, tablets, capsules, etc. may be used.
In addition, in the case of administration as a pharmaceutical, the administration method, dosage and number of administration can be appropriately selected depending on the age, weight and symptoms of the patient, but in the case of oral administration, the extract is 1 to 1000 mg / kg, preferably 20 to 100 mg / kg. It only has to be kg.
帰脾湯エキスは、アミロイドベータの活性部分配列（Ａβ(25-35））に誘発される軸索および樹状突起の萎縮に対し、顕著な改善作用を有する。
また、帰脾湯エキスは、Ａβ(25-35)のマウス脳室内投与より誘発される空間記憶障害を、正常レベルにまで回復させた。
これらのことから、帰脾湯エキスに代表される本発明の生薬の混合物は、既存の薬物には無い新規の作用様式を有し、アルツハイマー型記憶障害を予防および／または改善する薬物としてアルツハイマー型痴呆の治療に有用である。
次に実施例、試験例で本発明を説明するが、本発明はこれらに限定されない。
Kiyoto extract has a marked improvement effect on axonal and dendritic atrophy induced by an active partial sequence of amyloid beta (Aβ (25-35)).
Moreover, Kiyoto extract recovered the spatial memory impairment induced by intraventricular administration of Aβ (25-35) to the normal level.
From these facts, the herbal medicine mixture of the present invention typified by Kisaito extract has a novel mode of action not found in existing drugs, and Alzheimer type as a drug for preventing and / or improving Alzheimer type memory impairment. Useful for the treatment of dementia.
Next, although an example and a test example explain the present invention, the present invention is not limited to these.
実施例１
黄耆3g、人参3g、白朮3g、茯苓3g、遠志2g、大棗2g、当帰2g、甘草1g、生姜1.5g、木香1g、酸棗仁3g、龍眼肉3gを混合し、水600mLを加え、1時間煎じた。煎じ液を凍結乾燥し、粉末状の帰脾湯エキスを得た。
Example 1
3g yellow ginseng, 3g ginseng, 3g white ginseng, 3g ginger, 2g ginger, 2g toki, 2g toki, 1g licorice, 1.5g ginger, 1g wood incense, 3g acid soy sauce, 3g longan meat, add 600mL water Decocted for 1 hour. The decoction liquid was freeze-dried to obtain a powdered Kiyoto extract.
試験例１
［神経突起再伸展作用］
（方法）胎生18日齢のSDラットの大脳皮質神経細胞を分散培養した。10μMＡβ(25-35)を神経細胞に処置し障害を与えた。障害誘発後の神経細胞に対して帰脾湯エキスを処置した後、リン酸化型NF-H（軸索マーカー）、MAP2（樹状突起マーカー）に対する抗体を用いた免疫染色を行い、細胞当たりの軸索、樹状突起の長さを測定した。
Test example 1
[Nerite re-extension effect]
(Method) Cerebral cortical neurons of embryonic day 18 SD rats were dispersedly cultured. 10 μMAβ (25-35) was treated to damage neurons. After treatment with Kireito extract on the nerve cells after induction of injury, immunostaining using antibodies against phosphorylated NF-H (axon marker) and MAP2 (dendritic marker) was performed. The lengths of axons and dendrites were measured.
（結果）ラット大脳皮質神経細胞の培養開始3日後に、10μMＡβ(25-35)を処置した。4日後、軸索と樹状突起の著しい萎縮が認められた。ここに、帰脾湯エキスを100μg/mlで処置した、その5日後には軸索、樹状突起のいずれもが溶媒処置群に比べて有意に伸展した。 (Results) Three days after the start of culture of rat cerebral cortical neurons, 10 μMAβ (25-35) was treated. Four days later, significant atrophy of axons and dendrites was observed. Here, Kiyoto extract was treated with 100 μg / ml, and 5 days later, both axons and dendrites were significantly extended compared to the solvent-treated group.
試験例２
［空間記憶障害改善作用］
（方法）7週齢のddYマウス(雄)の右側脳室に、25 nmol Ａβ(25-35)を投与した。10日後から1日1回薬物を経口投与し14日間続けた。薬物投与を始めた7日後から、モーリス水迷路にて空間記憶の獲得試験を5日間行った。獲得試験の最終日で薬物投与を中止し、その3日後に水迷路にて空間記憶の保持試験を行った。
Test example 2
[Spatial memory impairment improvement effect]
(Method) 25 nmol Aβ (25-35) was administered to the right ventricle of a 7-week-old ddY mouse (male). The drug was orally administered once a day after 10 days and continued for 14 days. Seven days after the start of drug administration, a spatial memory acquisition test was conducted in the Morris water maze for 5 days. The drug administration was discontinued on the last day of the acquisition test, and a spatial memory retention test was conducted in the
（結果）25 nmolＡβ(25-35)の脳室内投与により、マウスの記憶獲得能力と記憶保持能力が有意に低下した。薬物を投与し始める、Ａβ(25-35)投与の7日後には既に、記憶障害が始まり、軸索、樹状突起、シナプス密度の減少が大脳皮質と海馬で顕著に認められ、この状態は少なくとも30日後まで継続することを確認している。
帰脾湯エキスを水に溶解し、100mg/kgあるいは1000mg/kgで連続経口投与した。いずれの投与量においても、帰脾湯エキス投与により記憶獲得能力が有意に回復した。記憶保持試験においてもいずれの投与量においても帰脾湯エキスによる有意な記憶保持能力の回復が認められた。いずれの試験においても、100mg/kg投与量の方がより作用が強く、対照群を凌ぐ記憶障害改善効果を示した。
(Results) Intraventricular administration of 25 nmol Aβ (25-35) significantly reduced the memory acquisition ability and memory retention ability of mice. 7 days after administration of Aβ (25-35), memory impairment began, and axons, dendrites, and synaptic density decreased markedly in the cerebral cortex and hippocampus. Confirmed to continue until at least 30 days later.
Kiyoto extract was dissolved in water and continuously administered orally at 100 mg / kg or 1000 mg / kg. At any dose, the ability to acquire memory was significantly recovered by administration of Kaiseito extract. In the memory retention test, significant recovery of memory retention ability was observed with Kiyoto extract at any dose. In any test, the dose of 100 mg / kg was more effective and showed an effect of improving memory impairment over the control group.
帰脾湯に代表されれる本発明の生薬混合物は、神経回路網形成作用および空間記憶障害改善作用を示し、脳内の神経回路網の破綻に起因する認識機能不全の症状を示すアルツハイマー型痴呆を治療するための漢方処方として有用である。 The herbal medicine mixture of the present invention typified by Kikisu-to exhibits Alzheimer-type dementia, which exhibits a neural network formation action and a spatial memory impairment improvement action, and exhibits symptoms of cognitive dysfunction due to the breakdown of the neural network in the brain. It is useful as a Kampo prescription for treatment.
Claims (3)
The preventive / ameliorating agent for Alzheimer's memory disorder according to claim 1 or 2, wherein the mixture is Kiyoto.
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| EP2042183A1 (en) * | 2007-09-27 | 2009-04-01 | Scindia AG | Herbal compositions |
| US20110318435A1 (en) * | 2010-06-24 | 2011-12-29 | Korea Institute Of Science And Technology | Composition comprising longan arillus extract or combined extract comprising the same for treating neurodegenerative disease |
| JP2012020964A (en) * | 2010-07-14 | 2012-02-02 | Arsoa Honsya Corp | Glutathione production promoter, and drug, food or cosmetic having glutathione production promoting action |
| CN102872239A (en) * | 2012-09-07 | 2013-01-16 | 李承平 | Qi-tonifying and yang-raising tablets |
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| CN104547865A (en) * | 2015-01-01 | 2015-04-29 | 曾子维 | Application of traditional Chinese medicine preparation in preparing medicine for treating senile dementia |
| CN104800303A (en) * | 2015-04-14 | 2015-07-29 | 齐齐哈尔医学院 | Traditional Chinese medicine composition for treating Alzheimer's disease as well as preparation method and application of traditional Chinese medicine composition |
| JP2015524827A (en) * | 2012-08-15 | 2015-08-27 | 戚 郁芬 | Pharmaceutical composition for increasing content and availability of cyclic adenosine monophosphate in the body, and preparation method thereof |
| CN105477496A (en) * | 2014-09-15 | 2016-04-13 | 北京创盈科技产业集团有限公司 | Traditional Chinese medicine combination containing cistanche and having function of memory improvement and preparation method of traditional Chinese medicine combination |
| JP2019182845A (en) * | 2018-04-02 | 2019-10-24 | 学校法人藤田学園 | Kynurenine aminotransferase 2 (kat2) inhibitor |
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| US20110318435A1 (en) * | 2010-06-24 | 2011-12-29 | Korea Institute Of Science And Technology | Composition comprising longan arillus extract or combined extract comprising the same for treating neurodegenerative disease |
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